Rise of Neurologic Manifestations During SARS-CoV-2 Omicron Wave in Children With COVID-19 : The Pediatric Infectious Disease Journal

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Rise of Neurologic Manifestations During SARS-CoV-2 Omicron Wave in Children With COVID-19

Dimopoulou, Dimitra MD, PhD; Dasoula, Foteini MD; Liaska, Marianthi MD; Eleftheriou, Irini MD; Maritsi, Despoina MD, PhD; Tsolia, Maria MD, PhD; Vartzelis, George MD, PhD

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The Pediatric Infectious Disease Journal 42(4):p e128-e129, April 2023. | DOI: 10.1097/INF.0000000000003826
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To the Editors:

Although COVID-19 pandemic continues to be a public health emergency, children have mostly asymptomatic or mildly symptomatic disease.1 The last wave caused by Omicron variant is characterized by less severe, but more contagious infection, resulting in higher rates of community transmission and increased numbers of pediatric COVID-19 hospitalizations.2 Before the Omicron variant, it has been reported that 16.7% of children with COVID-19 presented with mild and atypical neurologic manifestations and only 1% had severe neurologic complications.3 On the other hand, one large multicenter study reported that 40% of children with COVID-19 between January 2020 and April 2021 had at least 1 neurologic finding.4 Direct viral invasion of the nervous system or inflammatory activation may be the most likely neuropathophysiologic mechanisms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.5 To date, data about COVID-19–related neurologic manifestations in pediatric patients are scarce. However, it has been proposed that the Omicron variant may present a more epileptogenic profile.6 This study aims to evaluate the frequency, clinical characteristics, management and outcome of children with neurologic COVID-19–related symptoms during SARS-CoV-2 Omicron period and compare these findings with the previous waves.

This was a retrospective, single-center study that involved children 0–16 years of age with COVID-19 who were admitted to a tertiary Children’s hospital. Clinical characteristics and incidence of neurologic manifestations were compared between the 2 study periods, the first one before the emergence of Omicron variant (March 2020–December 31, 2021) and the second one, when Omicron variant was predominant (January 1, 2022–April 15, 2022). Data were analyzed using SPSS 20.0 software (IBM Corp., Armonk, NY, USA). Groups were compared with χ2 test for categorical variables and t test for quantitative variables. A P < 0.05 was considered statistically significant.

A total of 571 children were enrolled (first period: 311 children; second period: 260 children). COVID-19–related neurologic manifestations were observed in 25 children (8%) during the pre-Omicron period and in 58 children (22.3%) during the second period (P < 0.0001). The demographic and clinical characteristics of children with COVID-19–related neurologic manifestations during the 2 study periods are shown in Table 1. Febrile seizures significantly increased during the Omicron wave (P = 0.012), while headache was more frequent during the pre-Omicron period (P = 0.002). There was no difference in the other manifestations between the 2 periods. Electroencephalogram was performed in 9 children during the second period, and it was abnormal in 4 of them (44.4%), while magnetic resonance imaging was performed in 5 children, and it was normal in all of them. Treatment with anticonvulsants was administered for 3 months in 12 children, and it was discontinued without complications during the follow-up period in all.

TABLE 1. - Demographics and Clinical Characteristics of Children With COVID-19–related Manifestations During the 2 Study Periods
Characteristics 1st Period (N = 25) 2nd Period (N = 58) P
Sex (female/male) 11 (44%)/14 (56%) 25 (43.1%)/33 (56.9%) 0.94
Age, mean (SD) 10.1 years (5.46 years) 6.1 years (5 years) 0.0017
Medical history of neurological disorder 3 (12%) 5 (8.6%) 0.632
Febrile seizures 4 (16%) 26 (44.8%) 0.012
Afebrile seizures 3 (12%) 6 (10.3%) 0.824
Syncope/loss of consciousness 5 (20%) 12 (20.7%) 0.943
Febrile status epilepticus 0 (0%) 6 (10.3%) 0.095
Headache 13 (52%) 11 (19%) 0.002
Encephalopathy 0 (0%) 1 (1.7%) 0.509
Days of hospitalization, mean (SD) 3.96 days (2.6 days) 3.36 days (1.9 days) 0.243
ICU admission 0 (0%) 4 (6.9%) 0.178
Treatment with anticonvulsants 1 (4%) 11 (19%) 0.075
ICU indicates intensive care unit.
Bold indicates statistically significant value.

It was shown in this study that the period of Omicron variant predominance was characterized by an increased rate of neurologic manifestations among children with COVID-19. Febrile seizures were the most common manifestation and had a favorable outcome. Limitations of this study include its retrospective nature, the small sample size and the fact that imaging and electroencephalogram were not routinely performed in all patients but only upon request based on individual physician’s clinical decision. In addition, mean age was significantly lower during Omicron predominance, and this may account, at least in part, for the higher percentage of children with febrile seizures during the second study period since younger children are more prone to febrile seizures. Accordingly, mean age difference may also account to some degree for the higher percentage of children with headache during the first study period, as younger children may not be able verbalize or complain for headache. Further collaborative studies are required to determine the prevalence and the full spectrum of neurologic manifestations among SARS-CoV-2–infected children.


1. Lu X, Zhang L, Du H, et al. SARS-CoV-2 infection in children. N Engl J Med. 2020;382:1663–1665.
2. Cloete J, Kruger A, Masha M, et al. Paediatric hospitalisations due to COVID-19 during the first SARS-CoV-2 omicron (B.1.1.529) variant wave in South Africa: a multicentre observational study. Lancet Child Adolesc Health. 2022;6:294–302.
3. Panda PK, Sharawat IK, Panda P, et al. Neurological complications of SARS-CoV-2 infection in children: a systematic review and meta-analysis. J Trop Pediatr. 2021;67:fmaa070.
4. Fink EL, Robertson CL, Wainwright MS, et al. Prevalence and risk factors of neurologic manifestations in hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C. Pediatr Neurol. 2022;128:33–44.
5. Valderas C, Méndez G, Echeverría A, et al. COVID-19 and neurologic manifestations: a synthesis from the child neurologist’s corner. World J Pediatr. 2022;18:373–382.
6. Bova SM, Serafini L, Serati I, et al. Seizures may be an early sign of acute COVID-19, and the Omicron variant could present a more epileptogenic profile. Acta Paediatr. 2022111:1814–1815.

children; COVID-19; neurological manifestations; Omicron wave; severe acute respiratory syndrome coronavirus 2

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